This proposal involves the clinical testing of a pharmacologic agent in a smoking cessation trial. Clonidine, an alpha-2 agonist, has been shown to reduce symptoms in both acute opiate and alcohol withdrawal. Recently, it has been shown to reduce acute nicotine withdrawal as well. This proposal will test whether clonidine's ability to alter nicotine withdrawal is associated with an in- creased rate of success among a group of heavy cigarette smokers participating in a smoking cessation program. By use of a double- blind, placebo-controlled random assignment design, this proposal will test the ability of clonidine compared to a placebo to facilitate smoking cessation during a ten week treatment program and to examine if any meaningful advantage persists one year after the end of treatment. In addition, this proposal will test the hypothesis, that a past history of major affective disorder is a predictor of treatment outcome in smoking cessation and will explore the implications this has for new pharmacological treatment strategies in this group. The significance of this project stems from the enormous health hazard associated with cigarette smoking. Clonidine appears to be a new and promising aid to smoking cessation in heavy smokers who have tried to stop and failed on numerous other occasions. Among this group of severely addicted smokers our most successful presently available interventions have been, at best, seriously limited.